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Skeletal muscle mitochondrial oxidative phosphorylation function in idiopathic pulmonary arterial hypertension: in vivo and in vitro study

Lookup NU author(s): Sasiharan Sithamparanathan, Dr Mariana Rocha, Dr Jehill Parikh, Karolina Rygiel, Gavin Falkous, Dr John Grady, Dr Kieren Hollingsworth, Professor Mike TrenellORCiD, Professor Robert Taylor, Emeritus Professor Doug Turnbull, Professor Grainne Gorman, Emeritus Professor Nick Europe-Finner



This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).


© 2018, The Author(s) 2018. Mitochondrial dysfunction within the pulmonary vessels has been shown to contribute to the pathology of idiopathic pulmonary arterial hypertension (IPAH). We investigated the hypothesis of whether impaired exercise capacity observed in IPAH patients is in part due to primary mitochondrial oxidative phosphorylation (OXPHOS) dysfunction in skeletal muscle. This could lead to potentially new avenues of treatment beyond targeting the pulmonary vessels. Nine clinically stable participants with IPAH underwent cardiopulmonary exercise testing, in vivo and in vitro assessment of mitochondrial function by 31P-magnetic resonance spectroscopy (31P-MRS) and laboratory muscle biopsy analysis. 31P-MRS showed abnormal skeletal muscle bioenergetics with prolonged recovery times of phosphocreatine and abnormal muscle pH handling. Histochemistry and quadruple immunofluorescence performed on muscle biopsies showed normal function and subunit protein abundance of the complexes within the OXPHOS system. Our findings suggest that there is no primary mitochondrial OXPHOS dysfunction but raises the possibility of impaired oxygen delivery to the mitochondria affecting skeletal muscle bioenergetics during exercise.

Publication metadata

Author(s): Sithamparanathan S, Rocha MC, Parikh JD, Rygiel KA, Falkous G, Grady JP, Hollingsworth KG, Trenell MI, Taylor RW, Turnbull DM, Gorman GS, Corris PA

Publication type: Letter

Publication status: Published

Journal: Pulmonary Circulation

Year: 2018

Volume: 8

Issue: 2

Pages: 1-5

Print publication date: 01/04/2018

Online publication date: 25/05/2018

Acceptance date: 02/03/2018

ISSN (print): 2045-8932

ISSN (electronic): 2045-8940

Publisher: SAGE Publications Ltd


DOI: 10.1177/2045894018768290